我國科學(xué)家在長久以來尋求的新型男性避孕藥的研究方面取得了一項進展,，他們發(fā)現(xiàn)了男性的一些關(guān)鍵蛋白可以抑制精子的制造，而且可能成為未來男性避孕藥的新靶標,。他們的研究將發(fā)表在美國化學(xué)會于10月3日出版的《蛋白質(zhì)組研究雜志》月刊上,。
沙家豪及其同事指出，科學(xué)家不理解男性性激素睪酮的一個效應(yīng)——注射這種激素如何抑制了精子的制造,。此前的研究表明注射用睪酮和一種稱為左炔諾孕酮（LNG）的合成激素的聯(lián)用幾乎完全抑制了精子,，在這項研究的基礎(chǔ)上,，這組科學(xué)家設(shè)法弄清激素如何影響睪丸制造精子的細胞,。
在一項針對男性的新研究中，他們發(fā)現(xiàn)睪酮和左炔諾孕酮的聯(lián)用改變了人體的31種蛋白質(zhì)的制造,，相比之下,，只接受了睪酮的男性只有13種蛋白質(zhì)的制造發(fā)生了變化。這組科學(xué)家發(fā)現(xiàn)了一些蛋白質(zhì),，它們既可以作為新的男性避孕藥的靶標,，也可以作為治療不育的藥物的靶標。（生物谷Bioon.com）
生物谷推薦原始出處：
J. Proteome Res., 7 (9), 3984–3993, 2008. 10.1021/pr800259t
Proteomic Analysis of Testis Biopsies in Men Treated with Injectable Testosterone Undecanoate Alone or in Combination with Oral Levonorgestrel as Potential Male Contraceptive
Yugui Cui,†‡# Hui Zhu,†# Yefei Zhu,†⊥# Xuejiang Guo,† Ran Huo,† Xinghai Wang,§ Jiansun Tong,§ Lixin Qian,‡¶ Zuomin Zhou,† Yue Jia,∥ Yan-he Lue,∥ Amiya Sinha Hikim,∥ Christina Wang,∥ Ronald S. Swerdloff,∥ and Jiahao Sha*†
Laboratory of Reproductive Medicine, Department of Histology and Embryology, and Center of Clinical Reproductive Medicine, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China, Department of Reproductive Medicine, Jiangsu Family Planning Research Institute, Nanjing 210036, China, Division of Endocrinology, Department of Medicine, Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, Torrance, California 90502, and Jiangsu Provincial Center of Disease Control and Prevention, Nanjing 210009, China
Treatment with injectable testosterone undecanoate (TU) alone or in combination with oral levonorgestrel (LNG) resulted in marked decreases in sperm concentrations. In this study, we used proteomic analyses to examine the cellular/molecular events occurring in the human testis after TU or TU + LNG treatment. We conducted a global proteomic analysis of the human testicular biopsies before and at 2 weeks after TU alone or TU + LNG treatment. Proteins showing significant changes in expression were identified and analyzed. As a result, 17 and 46 protein spots were found with significant differential expression after the treatment with TU alone and TU + LNG, respectively. TU treatment changed the expression of heterogeneous nuclear ribonucleoprotein K (hnRNP K), proteasome inhibitor PI31 subunit (PSMF1), and superoxide dismutase [Mn] mitochondrial precursor (SOD2). These proteins inhibit “assembly”, induce cell death, and promote compensatory “cell survival” in the testis. After TU + LNG treatment, “proliferation/cell survival” and “apoptosis/death” were the predominant responses in the testis. TU + LNG treatment inhibited the expression of Prolyl 4-hydroxylase beta subunit (P4HB) and Annexin A2 (Annexin II). These proteins are involved in apoptosis and cell proliferation, respectively. TU + LNG treatment also enhanced the expression of SOD2 and Parvalbumin alpha (Pvalb). These two proteins may protect testicular cells against apoptosis/death and promote cell survival. In conclusion, TU and TU + LNG treatments suppress spermatogenesis through different pathways by changing the expression of different proteins. hnRNP K, PSMF1, SOD2, P4HB, Annexin II, and Pvalb, are key proteins that may be early molecular targets responsible for spermatogenesis suppression induced by hormone treatment.
